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Methylation tumor

Jian Zhang, Zi-Qi Zheng, Ya-Wei Yuan, Pan-Pan Zhang, Ying-Qin Li, Ya-Qin Wang, Xin-Ran Tang, Xin Wen, Xiao-Hong Hong, Yuan Lei, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma, Na Liu
DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo...
February 14, 2019: Neoplasia: An International Journal for Oncology Research
Om P S Patel, Ashutosh Arun, Pankaj K Singh, Deepika Saini, Sharanbasappa Shrimant Karade, Manish K Chourasia, Rituraj Konwar, Prem P Yadav
A series of new pyranocarbazole derivatives were synthesized via semi-synthetic modification of koenimbine (1a) and koenidine (1b) isolated from the leaves of Murraya koenigii. Among all, compound 3bg displayed significant anti-cancer activity against MDA-MB-231, DU145 and PC3 cell lines with the IC50 values of 3.8, 7.6 and 5.8 μM, respectively. It was also observed that the halogenated-benzyl substitution at N-9 position, C-3 Methyl and C-7 methoxy group on carbazole motif are favoured for anti-cancer activity...
February 7, 2019: European Journal of Medicinal Chemistry
Harmen van Andel, Kinga A Kocemba, Marcel Spaargaren, Steven T Pals
Aberrant activation of Wnt/β-catenin signaling plays a central role in the pathogenesis of a wide variety of malignancies and is typically caused by mutations in core Wnt pathway components driving constitutive, ligand-independent signaling. In multiple myelomas (MMs), however, these pathway intrinsic mutations are rare despite the fact that most tumors display aberrant Wnt pathway activity. Recent studies indicate that this activation is caused by genetic and epigenetic lesions of Wnt regulatory components, sensitizing MM cells to autocrine Wnt ligands and paracrine Wnts emanating from the bone marrow niche...
February 15, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Dipika R Mohan, Antonio Marcondes Lerario, Tobias Else, Bhramar Mukherjee, Madson Q Almeida, Michelle Vinco, Juilee Rege, Beatriz M P Mariani, Maria Claudia N Zerbini, Berenice B Mendonca, Ana Claudia Latronico, Suely K N Marie, William E Rainey, Thomas J Giordano, Maria Candida B V Fragoso, Gary D Hammer
PURPOSE: Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy with few therapies; however, patients with locoregional disease have variable outcomes. The Cancer Genome Atlas project on ACC (ACC-TCGA) identified that cancers of patients with homogeneously rapidly recurrent or fatal disease bear a unique CpG island hypermethylation phenotype, "CIMP-high." We sought to identify a biomarker that faithfully captures this subgroup. EXPERIMENTAL DESIGN: We analyzed ACC-TCGA data to characterize differentially regulated biological processes, and identify a biomarker that is methylated and silenced exclusively in CIMP-high ACC...
February 15, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Siva Prasad Panda, Uttam Prasad Panigrahy, Subhranshu Panda, Bikash R Jena
ETHNOPHARMACOLOGICAL RELEVANCE: The plant Tabebuia chrysantha (Jaq.) Nicholson (Bignoniaceae) is commonly known as "Golden Goddess" in the Southern part of India and "Golden Trumpet Tree " in Central America. Stems of this plant have been traditionally used for antioxidant, anti-inflammatory, antimicrobial and anticancer actions. AIM OF THE STUDY: To evaluate the antitumor activity of methanol extract of Tabebuia chrysantha stem (METC). MATERIALS AND METHODS: The in vivo antitumor potential of METC against Ehrlich Ascites Carcinoma (EAC) in Swiss albino mice was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters, biochemical parameters, and antioxidant parameters...
February 12, 2019: Journal of Ethnopharmacology
Jasmine Kaur, Abdelkader Daoud, Scott T Eblen
BACKGROUND: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis...
February 14, 2019: Current Molecular Pharmacology
Adriana Georgieva Bakalova, Rossen Todorov Buyukliev, Rositsa Petrova Nikolova, Boris Lubomirov Shivachev, Rositsa Asenova Mihaylovac, Spiro Mihaylov Konstantinov
BACKGROUND: The accidental discovery of cisplatin's growth-inhibiting properties a few decades ago led to resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been placed in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin...
February 13, 2019: Anti-cancer Agents in Medicinal Chemistry
H-X Pan, H-S Bai, Y Guo, Z-Y Cheng
OBJECTIVE: In this study, we aimed to investigate the expression profile of C2H2 zinc finger (ZNF) 860 (ZNF860) in gastric cancer (GC), its prognostic significance and its potential regulatory network in GC. PATIENTS AND METHODS: The level-3 data in the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) was acquired for a secondary analysis, in which clinicopathological, genetic and survival data from 415 GC patients were collected. RESULTS: The gastric cancerous tissues had significantly upregulated ZNF860 expression...
January 2019: European Review for Medical and Pharmacological Sciences
Natalia Pinello, Stephanie Sun, Justin Jong-Leong Wong
N6 -methyladenosine (m6 A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal, cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m6 A methylation has been implicated in the development and maintenance of diverse human cancers. Altered m6 A levels affect RNA processing, mRNA degradation, and translation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studies have reported that the abnormal expression of m6 A regulatory enzymes affects m6 A abundance and consequently dysregulates the expression of tumor suppressor genes and oncogenes, including MYC , SOCS2 , ADAM19 , and PTEN ...
November 2018: Cancer Biology & Medicine
Yu Ren, Yun-Fei Wang, Jing Zhang, Qi-Xue Wang, Lei Han, Mei Mei, Chun-Sheng Kang
BACKGROUND: Nearly 25% of long intergenic non-coding RNAs (lincRNAs) recruit chromatin-modifying proteins (e.g., EZH2) to silence target genes. HOX antisense intergenic RNA (HOTAIR) is deregulated in diverse cancers and could be an independent and powerful predictor of eventual metastasis and death. Yet, it is challenging to develop small molecule drugs to block activity of HOTAIR with high specificity in a short time. RESULTS: Our previous study proved that the 5' domain, but not its 3' domain, was the function domain of HOTAIR responsible for tumorigenesis and metastasis in glioblastoma and breast cancer, by recruiting and binding EZH2...
February 14, 2019: Clinical Epigenetics
Boran Pang, Qin Wang, Shipeng Ning, Junqiang Wu, Xingda Zhang, Yanbo Chen, Shouping Xu
BACKGROUND: The landscape and biological functions of tumor suppressor long noncoding RNAs in breast cancer are still unknown. METHODS: Data from whole transcriptome sequencing of 33 breast specimens in the Harbin Medical University Cancer Center cohort and The Cancer Genome Atlas was applied to identify and validate the landscape of tumor suppressor long noncoding RNAs, which was further validated by The Cancer Genome Atlas pancancer data including 33 cancer types and 12,839 patients...
February 14, 2019: Journal of Experimental & Clinical Cancer Research: CR
A-Reum Kim, Jee Young Sung, Seung Bae Rho, Yong-Nyun Kim, Kyungsil Yoon
Suppressor of Variegation 3-9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G₁ cell cycle arrest...
February 15, 2019: Biomolecules & Therapeutics
Mohammad Alzrigat, Helena Jernberg-Wiklund, Jonathan D Licht
The enhancer of zeste homolog 2 (EZH2) is the enzymatic subunit of the polycomb repressive complex 2 (PRC2) that exerts important functions during normal development as well as disease. PRC2 through EZH2 tri-methylates histone H3 lysine tail residue 27 (H3K27me3), a modification associated with repression of gene expression programs related to stem cell self-renewal, cell cycle, cell differentiation, and cellular transformation. EZH2 is deregulated and subjected to gain of function or loss of function mutations, and hence functions as an oncogene or tumor suppressor gene in a context-dependent manner...
September 2018: Epigenomes
Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Shunsaku Takayanagi, Ryohei Otani, Takahide Nejo, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Mayu Omata, Fumi Higuchi, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Nobuhito Saito, Hiroyuki Aburatani, Akitake Mukasa
To elucidate the mechanisms of malignant progression of lower-grade glioma, molecular profiling using methylation array, whole-exome sequencing, and RNA sequencing was performed for 122, 36 and 31 gliomas, respectively. This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP)...
February 13, 2019: Scientific Reports
Rajni Kant, Chia-Hung Yen, Jung-Hsien Hung, Chung-Kuang Lu, Chien-Yi Tung, Pei-Ching Chang, Yueh-Hao Chen, Yu-Chang Tyan, Yi-Ming Arthur Chen
Glycine-N-methyl transferase (GNMT) a tumor suppressor for hepatocellular carcinoma (HCC) plays a crucial role in liver homeostasis. Its expression is downregulated in almost all the tumor tissues of HCC while the mechanism of this downregulation is not yet fully understood. Recently, we identified 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (PGG) as a GNMT promoter enhancer compound in HCC. In this study, we aimed to delineate the mechanism by which PGG enhances GNMT expression and to investigate its effect on GNMT suppression in HCC...
February 13, 2019: Scientific Reports
Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chang Dong Yeo, Chan Kwon Park, Young Kyoon Kim, Tae-Jung Kim, Seong-Beom Lee, Sug Hyung Lee, Jong Y Park, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim
BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed...
February 13, 2019: BMC Cancer
Yanghao Hou, Jorge Pinheiro, Felix Sahm, David E Reuss, Daniel Schrimpf, Damian Stichel, Belén Casalini, Christian Koelsche, Philipp Sievers, Annika K Wefers, Annekathrin Reinhardt, Azadeh Ebrahimi, Francisco Fernández-Klett, Stefan Pusch, Jochen Meier, Leonille Schweizer, Werner Paulus, Marco Prinz, Christian Hartmann, Karl H Plate, Guido Reifenberger, Torsten Pietsch, Pascale Varlet, Mélanie Pagès, Ulrich Schüller, David Scheie, Karin de Stricker, Stephan Frank, Jürgen Hench, Bianca Pollo, Sebastian Brandner, Andreas Unterberg, Stefan M Pfister, David T W Jones, Andrey Korshunov, Wolfgang Wick, David Capper, Ingmar Blümcke, Andreas von Deimling, Luca Bertero
Papillary glioneuronal tumor (PGNT) is a WHO-defined brain tumor entity that poses a major diagnostic challenge. Recently, SLC44A1-PRKCA fusions have been described in PGNT. We subjected 28 brain tumors from different institutions histologically diagnosed as PGNT to molecular and morphological analysis. Array-based methylation analysis revealed that 17/28 tumors exhibited methylation profiles typical for other tumor entities, mostly dysembryoplastic neuroepithelial tumor and hemispheric pilocytic astrocytoma...
February 13, 2019: Acta Neuropathologica
Katie Storey, Kevin Leder, Andrea Hawkins-Daarud, Kristin Swanson, Atique U Ahmed, Russell C Rockne, Jasmine Foo
Tumor recurrence in glioblastoma multiforme (GBM) is often attributed to acquired resistance to the standard chemotherapeutic agent, temozolomide (TMZ). Promoter methylation of the DNA repair gene MGMT (O6 -methylguanine-DNA methyltransferase) has been associated with sensitivity to TMZ, whereas increased expression of MGMT has been associated with TMZ resistance. Clinical studies have observed a downward shift in MGMT methylation percentage from primary to recurrent stage tumors; however, the evolutionary processes that drive this shift and more generally the emergence and growth of TMZ-resistant tumor subpopulations are still poorly understood...
February 2019: JCO Clinical Cancer Informatics
Akshitkumar M Mistry, David J Wooten, L Taylor Davis, Bret C Mobley, Vito Quaranta, Rebecca A Ihrie
Whether patients with glioblastoma that contacts the ventricular-subventricular zone stem cell niche (VSVZ + GBM) have a distinct survival profile from VSVZ - GBM patients independent of other known predictors or molecular profiles is unclear. Using multivariate Cox analysis to adjust survival for widely-accepted predictors, hazard ratios (HRs) for overall (OS) and progression free (PFS) survival between VSVZ + GBM and VSVZ - GBM patients were calculated in 170 single-institution patients and 254 patients included in both The Cancer Genome (TCGA) and Imaging (TCIA) atlases...
February 12, 2019: Scientific Reports
Xuanrong Sun, Longchao Zhang, Mengshi Gao, Xiangjie Que, Chenfeng Zhou, Dabu Zhu, Yue Cai
Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles...
February 11, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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